Ethers of polychlorinated benzonitriles

ABSTRACT

NOVEL ETHERS ARE PREPARED VIA THE INTERACTION OF PENTACHLOROBENZONITRILE WITH ALKALI METAL SALTS OF SATURATED ALIPHATIC ALCOHOLS SUCH AS METHANOL, ETHANOL, PROPANOL, TBUTANOL AND AROMATIC ALCOHOLS SUCH AS PHENOL, OR SUBSTITUTED PHENOLS. THESE NEW COMPOUNDS HAVE BIOLOGICAL ACTIVITY AND ARE ALSO USEFUL AS CHEMICAL INTERMEDIATES.

United Stat s Paw?" 5 3,798,255 Patented Mar. 19, 1974 3,798,255 ETHERS0F POLYCHLORINATED BENZONITRILES Lewis William Watts, Jr., Austin, Tex.,assignor to Jeiferson Chemical Company, Inc., Houston, Tex. No Drawing.Filed May 3, 1971, Ser. No. 139,868 Int. Cl. C07c 121/52 US. Cl. 260-465F 1 Claim ABSTRACT or THE DISCLOSURE Novel ethers are prepared via theinteraction of pentachlorobenzonitrile with alkali metal salts 'ofsaturated'aliphatic alcohols such as methanol, ethanol, propanol,tbutanol and aromatic alcohols such as phenol or substituted phenols.These new compounds have biological 'activity and are also useful as.chemical intermediates.

BACKGROUND OF THE INVENTION Field of the invention The inventionpertains to new compositions of matter, their synthesis and theirbiological use.

Description of prior art salt-of an alcohol or a phenol. The alkalimetal alcoholates or phenolates are derived from saturated aliphaticalcohols such as methanol, ethanol, propanol, or t-butanol or aromaticalcohols such as phenol or substituted phenols by any of the methodsknown to those skilled in the art,

e.g., from the alcohol and alkali metal, the alkali metal Beck, G.,Degener, E., and Heitzer, H., Liebigs Ann.

Chem., 716, 47 (1968) discuss the chemistry of pentachlorobenzonitrile.Of special interest in this paper are-the observations recordedconcerning the di-alkylation of pentachlorobenzonitrile with amines.Such reactions were observed to:

(a) Proceed only under rather drastic conditions;

(b) Give rise to the desired'products in only moderate yields; V

(c) Often be accompanied by partial dechlo'rina t'ion.

It was quite surprising to discover that one,.two, or

SUMMARY OF THE INVENTION New compounds of the formula wherein A is alkyl1 to 8 carbon atoms or-aryl, x is2, 3, or 4 and y is l, 2 or 3 areuseful biological: chemicals.

The compounds are prepared by the interaction of pentachlorobenzonitrilewith alkali metal salts of alcohols or phenols whereinthe alcoholates orphenolates are derived from saturated aliphatic alcoohls such asmethanol, ethanol, propanol or t-butanol or aromatic alcohols 'such asphenol or substituted phenols.

DESCRIPTION OF THE PREPERLREOTM,

EMBODIMENTS, a

1 1 The new ethers of my'invention' are prepared by the in- L teractionof p'entachlorobenionitr ileand arfalkali metal hydride, or the alkalimetal hydroxide. The preformation of the alkali metal alcoholate orphenolate is probably not necessary for the successful completion of thereactions described below. Amines such as pyridine which function ascatalysts may be used in the synthesis of the compounds of my invention.The following examples illustrate individual preparations of compoundsof my invention but are not to be construed as limitative.

EXAMPLE 1 Preparation of trimethoxy-dichlorobenzonitrile Into a 2-literglass flask was placed 66.0 grams (0.24 mole) pentachlorobenzonitrileand 1.5 liters pyridine. After cooling this solution to 5 C., 218 gms.(0.99 mole) of a 25% sodium methoxide in methanol solution was added viaa dropping funnel at a rate such that the temperature of the reactantsdid not exceed 25 C. Following completion of the addition, thetemperature was increased to 50 C. and stirring continued for 30minutes. When cool, the crude reaction mixture was treated with a large"volume of cold water, then filtered. The almost whitetrimethoxy-dichlorobenzonitrile of the formula CIN weighed 47.9 gms.;analysis of this material by gas liquid chromatography (GLC) indicatedthe purity to be i.e., vonly one compound was present. Recrystallizationfrom petroleum ether gave long white needles, M.P.

The nuclear magnetic resonance (NMR) spectrum consisted of two sharpsinglets at 4.1 (6H) and 4.0 p.p.m. (3H) while the infrared (IR)spectrum showed a characteristic nitrile absorption at 2222. cm and anether band at 1099. cm- Further characterization of the reaction productwas provided by mass spectral analysis; calculated mass number fortrimethoxy-dichlorobenzonitrile, 261. Observed parent molecular ion, 261m/e.

EXAMPLE 2 Synthesis of trimethoxy-dichlorobenzonitrile To a solution of3.7 gms. (0.014 mole) methoxytetrachlorobenzonitrile in 200 ml. ofpyridine was added in one portion 7.0 gms. (0.033 mole) of a 25% sodiummethoxide in methanol solution. After warming at 50C. for 15 minutes thereaction mixture was treated with a large quantity of cold water, thenfiltered. The infrared spectrum of the dry product (light tan solid, 3.5gms., 97.8% yield) was identical with the spectrum oftrimethoxy-dichlorobenzonitrile prepared in Example 1, above.

EXAMPLE 3 Synthesis of methoxy-tetrachlorobenzonitrile To acold (4 C.)solution of 66.0 gms. (0.24'mole) pentachlorobenzonitrile in 1200 ml.pyridine was added dropwise with stirring 57.0 gms. (0.26 mole) of a 25%sodium methoxide-methanol solution. After addition of the sodiummethoxide hadbeen completed, the reaction temperature was increased to35 C. and maintained at that temperature for 30 minutes. The coolreaction mixture was poured into a large excess of 'water, filtered, and

the filtrate discarded. The solid was dissolved in chloroform, treatedwith MgSO filtered, then placed under reduced pressure until free ofsolvent. The weight of the white, rather flufify solid was 59.2 gms.,which corresponds to a 92.1% yield of methoxy-tetrachlorobenzoni trile,a compound of the formula.

Preparation of methoxy-tetrachlorobenzonitrile A mixture of 11.0 gms.(0.04 mole) pentachlorobenzonitrile in 200 m1. dioxane was placed in a500 ml. glass reaction vessel. A solution of 25% sodium methoxide inmethanol (9.5 gms., 0.042 mole) was quickly added in one portion withvigorous stirring of the reaction mixture. After the orange coloredmixture had been heated at 55 C. for 30 minutes, it was poured intowater, then filtered. In this manner there was isolated 10.7 gms. (98.8%yield) of pale yellow methoxy-tetrachlorobenzonitrile.

EXAMPLE 5 Preparation of dimethoxy-trichlorobenzonitrile A solution of114.0 gms. (0.528 mole) of a 25% sodium methoxide-methanol in 100 ml.absolute methanol was added dropwise to a stirred solution of 66.0 gms.(0.25 mole) pentachlorobenzonitrile in 1500 cc. of pyridine. The rate ofthe sodium methoxide addition was adjusted so that the originaltemperature of the solution (20 C.) was maintained until the additionhad been completted. Thereafter, the reaction mixture was stirred at 35C. for 60 minutes. Using the same product recovthe mixture was extractedtwo times with ether. The com- "bined ether extracts were dried overMgSO ,-filtered, then evaporated under reduced pressure. Both the NMRand infrared spectrum of this material were consistent with the proposedformula, viz,

C 0- (:1 CH1 C 3 7 w EXAMPLE 7 Preparation ofethoxy-tetrachlorobenzonitrile A solution of sodium ethoxide in ethanol,prepared by adding 4.6 g. sodium to 150 m1. absolute ethanol, wasquickly added to a mixture consisting of 55.0 g.pentachlorobenzonitrileand 260 ml. pyridine. To avoid reactiontemperatures in excess of 75 C., ice water cooling was required. v,

Following the usual procedure, there was isolated a colorlesscrystalline material (54.9 g.) which was shown to beethoxy-tetrachlorobenzonitrile of the formula ery technique as describedfor the isolation of the monomethoxy derivative in'Example 3, 55.8 gms.of a white crystalline solid was obtained; the yield ofdimethoxytrichlorobenzonitrile of the formula CHaM 3 was 94.5%.Crystallization from carbon tetrachloride gave fine needles, M.P.105.5107 C.

Analysis.Calculated for C H Cl NO 39.91% chlorine, 5.26% nitrogen.Found: 39.9% chlorine, 5.18% nitrogen.

Calculated mass number, 265.

Observed parent molecular ion, 265 m./e.

Infrared spectrum: 2242 cm.-1, nitrile; 1101 cm.-1, ether.

' EXAMPLE 6 Preparation of t-butoxy-tetrachlorobenzonitrile To asolution of 27.5 gms. (0.1 mole) pentachlorobenzonitrile in 200 ml.tetrahydrofuran was added 11.2 gms. (0.1 mole) potassium t-butoxide.After stirring the resulting mixture at 25 C. for 1 hr., it was allowedto stand overnight. Following the addition of ice cold water,

O CHzCHs colorless needles from heptane-ether, M.P. 8191 C.

' Analysis.Calculated for CgH Cl NO (284.96); 37.94% C, 1.77% H, 49.77%Cl, 4.92% N, 5.62% 0. Found: 37.44% C, 1.54% H, 5.14% N.

EXAMPLE 8 Preparation of phenoxy-tetrachlorobenzonitrile A mixture of6.8 gms. KOH, 9.8 gms. phenol, and 300 ml. toluene was heated until ml.of toluene had distilled. To the resulting mixture was added 250 m1.pyridine followed by 27.0 gms. pentachlorobenzonitrile. After heating at50 C. for two hours, the crude reaction product was poured into water.Filtration of the resulting mixture provided 28.0 gms.phenoxy-tetrachlorobenzonitrile of the formula Crystallization fromheptane-toluene gave small colorless plates, M.P. 196-199 C.

An'alysis.--Oa1culated for C H CI NO (333.00); 46.89% C, 1.51% H,42.59%C1, 4.21% N, 4.80% 0. Found: 47.00% C, 1.46% H, 42.57% Cl, 4.03%N.

Both the NMR and IR were consistent with the proposed formulation.

Comparable results are obtained in preparing other ethers within thescope of my invention.

The compounds of my invention are useful biological chemicals,particularly in controlling undesirable vegetation, which is illustratedby the data in the tables, below. The data in Table I showmonomethoxy-tetrachlorobenzonitrile and dimethoxy-trichlorobenzonitrileto be post emergent herbicides against morning glory (of the bindweedfamily) while non-phytotoxic to corn. The data in Table 2 showmonomethoxy-tetrachlorobenzonitrile to be a pre-emergent herbicideagainst pigweed and setaria while non-phytotoxicito corn anddimethoxy-trichlord 5" 6 benzinitrile to be a pre-emergent herbicideagainst pig- When it was assured that all emergence had occurred, weedand Johnson grass while non-phytotoxic to corn as determined by thecheck, emergence counts were made and tomato. The data in Table 3 showmonomethoxyon all crops. At the end of 14 to 1'6 days,-a phytotoxicitytetrachlorobenzonitrile, dimethoxy-trichlorobenzonitrile reading wasmade on the various crops indicating the andtrimethoxy-dichlorobenzonitrile to exert fungicidal extent of damage notonly by the stand of the crops, but

activity against early blight on tomatoes and to be non- 5 also theextent of damage to the emerged seedlings. Phytophytotoxic to tomatoplants. The data in Table 4 show toxicity data are recorded on a scaleof to 10 in which trimethoxy-dichlorobenzonitrile to be an activefungicide 0 indicated no injury to the other extremewhere 10 indiagainstsclerotium-cuks. Comparable results to those in cates that the plantswere killed.

TABLE 2.PRE-EMERGENCE HERBICIDAL EVALUATION Pig Johnson Morning vCompound Variable weed Setarla grass Milo glory Tomato CornMonomethoxytetrachlorobenzonltrile. Percent emergence.- 10 3O 85 85 8510 5 I Rating 7 21'. 0 0 10 08 Dimethoxytrlehlorobenzonitrile Percentemergence.- 50 50 60 i 85 85 5 Rating 5 til 8 41 0 0 80 I=Inhlblted.

the tables, below, are obtained in testing other ethers FOLIAR'FUNGICIDE SCREENING USING EARLY within the scope of my invention.BLIGHT ON T OMATOES POST EMERGENQE SCREEN The objective of this test wasto'evaluate the compounds The purpose of this test recorded in Table 1was to of the invention as foliar fungicide protectants using early makefoliar application to a series of crops, under standblight (Alternariasolam) on tomatoes. The compounds ard conditions, to evaluate thepost-emergence herbicidal were applied to tomato foilage (variety BonnieBest) at activity of the compounds of the invention. The crops emadosage of 500 parts per million (p.p.m.) while the ployed in thispost-emergence herbicidal evaluation were plants were being rotated on aturn-table. Effective pigweed, setaria, morning glory, tomatoes, Johnsongrass, amounts range from 100 to 500 ppm. The spray deposit oats, wheat,milo, red kidney beans and corn. Weed species was allowed to thoroughlydry on the foilage and then were approximately 2" in height at time ofspraying, corn sprayed with a spore suspension of Alternaria solaniagain. about 4" and wheat and oats 3". Tomatoes and red kidney while theplants were being rotated on a tum-table. Imbeans were approximatelythree weeks old. The com mediately after inoculation the plants weretransferred to pounds were extended in water to obtain the desired finala constant temperature-humidity cabinet for a period of suspension. Thecompounds were screened at 5' pounds 24 hours;At the end of this timethe plants were moved per ac e (active ingredient) calculated onv a.broadcast to the. greenhouse bench. Final data was recorded five tobasis. Efiective amounts range from 1 to'l5 pounds per six days afterincubation at which time the untreated acre. The plants were scored forphytotoxicity 10 to. 12 check controls were showing some 150 to 250early blight days after spray application. Phytotoxicit'y' ratings. are",..lesions per "three sets of three terminal leaflets per plant. basedupon a scale of 0 to 10 in which 0 indicates no injury Percent controlwas recorded as the percentage of lesions to the other extreme where 10indicates that the plants occurring on thetreated plants over the numberof lesions were killed. 1 occurring onthe untreated controls.

TABLE 1.-POST EMERGENCE HERBIC ID AL EVlLUATION PHYTOTOXICITY RATINGSRed Pig Johnson Morning kidney Compound weed Setarla grass Milo gloryTomato Oats Wheat beans Corn Monomethoxy-tetrachlorobenzonltrlle 0 0 0II 9 8M 0 0 0 0 Dimethoxytrichlorobenzonltrile 0 0 0 0 10 3 0 0 0 0NOTE.I=Inhibited. M=Morphegenlc.

PRE'EMERGENCE HERBICIDAL EVALUATION TABLE 3.EVALUA'1ION AS FOLIAR PROTECTANT FUN or- The purpose of this test recorded in Table 2 was to CIDESUSING EARLY BLIGHTAS THE TEST ORGANISM determine herbicidal activity ofcompounds of the inven- Percent tion by a soil pre-emergence evaluationon seven crops. i g i ag Flats were planted to the desired crops to adepth of Compound -D- co t o at approximately one-half inch. The cropsemployed were Monomethoxfietmmombenzommlmn 5m 50 0 pigweed, tomato,morning glory, Johnson grass, milo, rtflc o e o itrile 5 25 0Trlmethoxy-dlchlorobenzonitrile 500 30 0 setaria and corn. Care wasemployed in using a consistent amount of soil in the bottom of theflats, in the use of a templet in the manking 0f the seed rows, in theamount SOIL FUNGICIDE SCREENING AGAINST m OC Of seeds used, and in theamount Of soil on top of the seeds, in the interest of uniformity fromday to day and test to test. The compounds were initially The P p of thetest was evalllafe funglcldal screened at a dosage of 10 pounds ofactive ingredient a ivi y 0f rim thoxyichlorobenzomtnle by means of eracre, Effective amounts range fro 3 to 15 pounds discrete Soil-BorneFungi. The test organisms were raised per acre. The compounds wereextended in water and in sterile soil cultures to which had been added20% by 2.50 ml. of such a suspension uniformly distributed over weightof corn meal. The soil to be used for dilution pureach flat. The flatswere immediately transferred to the poses was separately sterilized bymeans of methyl brogreenhouse and covered for a period of three days sothat mide. The pure culture soil to be used for test purposes additionalwatering was not required until some of the was then prepared byadmixing 10% by weight of the test plants had begun to make theirappearance above ground. organism inoculum with by welght of sterilizedSO11.

control-wasreadily evident visually. It is easy-to recognize degrees ofcontrol based upon the'extent of mycelial growth and a rating scale'of'lO too is used, in which indicates no mycelial growth to the otherextreme where 0 indicates that no control is present.

8. I claim: 1. A process for preparing compounds of the formula 10wherein A is alkyl of 1 to 8 carbon atoms or phenyl, x

is 2, 3 or 4,.and, correspondingly, y is 1, 2, or 3 the sum of x andy'being' 5; "which'comprise's mixing and reacting. pentachlorobenzonitrile with an alkali metal salt of an alcohol of 1 to 8 carbon atomsper molecule or phenol at a temperature of from about 4 C. to about'75C.

TABLE 4.SOIL FUNGICIDAL EVALUATION OF CANDIDATE MATERIALS Pythium-peasRhizoctonla-beets Sclerotium-cuks Fusarium-tomato BW/S, MYG Percent MYCPercent MYC Percent MYC Percent Compound p.p.m. growth stand growthstand growth stand growth stand Tiimethoxy-diehlorobenzonltrile 0 0 7'References Cited UNITED STATES PATENTS OTHER REFE R ENQES Vasilevskayaet al.', J. Org. Chem. USSR. 6, pp.

c. A., vol. 68, 19 63,515ed0h 59 336(I.C.D. lstd.). I RODD ChemistryofTJ Carbon ,Compounds, 'v'ol. 3-A (aromatic compounds), 1954, pp.114-115 Y JOSEPH P. BR'USTfPrii nary Examiner UNITED STATES PATENTOFFICE CERTIFICATE OF CORRECTION Patent No. 3,798,255 Dated March 19,1974 Lewis William Watts, Jr. Assignor to Jefferson Chemical Company,Inc.

Houston, Texas, a corporation of Delaware It iscertified that errorsappear in the aboveidentified patent and that said Letters Patent arehereby corrected as shown below:

In column 1, line 48, "an" should read and column 1, line 65, "alcoohls"should read alcohols In column 3, line 47, "completted" should readcompleted In columns 5 and 6, Table 2, last-column,

"Corn 7 should read Corn Signed and sealed this 17th day of September1974.

(SEAL) Attest:

MCCOY M. GIBSON JR. C. MARSHALL DANN Attesting Officer 7 Commissioner ofPatents

